Heme/Onc - First Aid Flashcards
1
Q
Erythrocyte Features
A
-carries O2 to tissues and CO2 to lungs -anucleate, biconcave -large surface area to volume ratio for rapid gas exchange -life span = 120 days -uses glucose for energy
2
Q
The membrane of erythrocytes contains…
A
chloride-HCO3- antiporter which allows RBCs to export HCO3- and transport CO2 from the periphery to the lungs for excretion.
3
Q
A reticulocyte is…
A
an immature erythrocyte; a marker of erythroid proliferation.
4
Q
Anisocytosis
A
varying size
5
Q
Poikilocytosis
A
varying shape
6
Q
Platelet (thrombocyte) features
A
-invovled in primary hemostasis -small cytoplasmic fragment derived from megakaryocytes -life span = 8-10 days
7
Q
When a platelet is activated by endothelial injury, it will…
A
aggregate with other platelets and interact with fibrinogen to form a platelet plug.
8
Q
Platelets contain…
A
dens granules (ADP and calcium) and alpha granules (vWF and fibrinogen).
9
Q
Thrombocytopenia or decreased platelet function results in…
A
petechiae.
10
Q
vWF receptor
A
GPIb
11
Q
Fibrinogen receptor
A
GPIIb/IIIa
12
Q
Leukocytes are divided into…
A
granulocytes (neutrophils, eosinophils, basophils) and mononuclear cells (monocytes and lymphocytes).
13
Q
Normal Leukocyte level
A
4000-10000
14
Q
WBC differential from highest to lowest
A
Neutrophils Like Making Everything Better Neutrophils (54-62%) Lymphocytes (25-33%) Monocytes (3-7%) Eosinophils (1-3%) Basophils (0-.75%)
15
Q
Neutrophils are…
A
an acute inflammatory response cell seen in bacterial infections. -phagocytic -multilobed
16
Q
Small neutrophils with more numerous specific granules contain…
A
ALP, collagenase, lysozyme and lactoferrin.
17
Q
Larger neutrophils with less numerous azurophilic granules contain…
A
proteinases, acid phophatase, myeloperoxidase and beta-glucoronidase.
18
Q
Hypersegmented PMNs (5 or more lobes) are seen in…
A
vitamin B12/folate deficiency.
19
Q
Increased band cells (immature neutrophils) reflect states of…
A
myeloid proliferation (bacterial infections, CML).
20
Q
Monocytes differentiate into…
A
macrophages in tissues.
21
Q
Monocyte features
A
-large, kidney-shpaed nucleus -“frosted glass” cytoplasm
22
Q
Macrophages act to…
A
phagocytose bacteria, cellular debris and senescent RBCs and scavenge damaged cells and tissue.
23
Q
Macrophages are activated from monocytes via…
A
gamma-interferon.
24
Q
Macrophages can function as…
A
antigen presenting cells via MHC II.
25
Surface marker for macrophages
CD14
26
Macrophages are an important component of...
granuloma formation.
27
Eosinophils defend against...
helminthic infections (w/ major basic protein).
28
Eosinophils features
-bilobate nucleus -packed with large eosinophilic granules -highly phagocytic for Ag-Ab complexes
29
Eosinophils produce..
histaminase and arylsulfatase (these help limit rxn following mast cell degranulation).
30
Causes of eosinophilia
NAACP N: neoplasia A: asthma A: allergies C: CT disorders P: parasites
31
Basophils mediate...
allergic rxns.
32
Basophil features
densely basophilic granules containing heparin (anticoagulant), histamine (vasodilator) and leukotrienes.
33
Isolated basophilia is rare but can be a sign of...
myeloproliferative disease (particularly CML).
34
Mast cells mediate...
allergic rxn in local tissue. (resemble basophils)
35
Mast cells can bind...
the Fc portion of IgE to the membrane. IgE cross-links upon Ag binding, causing degranulation, which releases heparin, histamine, and eosinophilic chemotactic factors.
36
Mast cells are involved in...
type I HSR.
37
Mast cell degranulation is prevented by...
cromolyn sodium (used for asthma prophylaxis).
38
Dendritic cells are...
highly phagocytic APCs that function as the link between the innate and adaptive immune systems.
39
Dendritic cells express...
MHC class II and Fc receptors on the surface.
40
Dendritic cells of the skin are called...
Langerhans cells.
41
Lymphocyte appearance
round, densely staining nucleus with a small amount of pale cytoplasm
42
B lymphocytes arise from...
stem cells in bone marrow, mature there and then migrate to peripheral lymphoid tissue (follicles of LNs, white pulp of spleen).
43
When Ag is encountered, B cells will...
differentiate into plasma cells that produce Abs and memory cells.
44
B cells can function as...
an APC via MHC II.
45
T lymphocytes originate from...
stem cells in the bone marrow but mature in the thymus.
46
The costimulatory signal necessary for T-cell activation is...
CD28.
47
The primary target of HIV is...
CD4+ helper T cells.
48
Plasma cell appearance
eccentric nucleus clock-face chromatin abundant RER well-developed Golgi apparatus
49
Universal recipient of RBCs
AB blood group
50
Universal donor of plasma
AB blood group
51
Universal donor of RBCs
O blood group
52
Universal recipient of plasma
O blood group
53
Rh- mothers who are exposed to fetal Rh+ blood (oftenduring delivery) may make...
anti-Rh IgG. In subsequent pregnancies, anti-Rh IgG crosses the placenta causing hemolytic disease of the newborn (erythroblastosis fetalis).
54
Rho(D) immune globulin is given for...
mothers during every pregnancy to prevent intial sensitizaiton of Rh- mother to Rh antigen.
55
Warfarin acts by...
inhibiting the enzyme vitamin K epoxide reductase to prevent maturation of coagulation factors.
56
Neonates lack enteric bacteria which produce...
vitamin K.
57
Vitamin K deficiency leads to...
decreasd synthesis of factors II, VII, IX, X, protein C and S.
58
vWF carries/protects...
factor VIII.
59
Antithrombin inhibits...
activated forms of factors II, VII, IX, X, XI, XII.
60
Heparin enhances...
the activity of antithrombin.
61
Principal targets of antithrombin
thrombin and factor Xa
62
Factor V Leiden mutation produces...
a factor V resistant to inhibition by activated protein C.
63
tPA is used clinically as...
a thrombolytic. It converts plasminogen to plasmin which then causes fibrinolysis.
64
A normal platelet aggregation response is not seen in...
von Willebrand disease.
65
Acute phase reactants in plasma (fibrinogen) can cause...
RBC aggregation, thereby increasing RBC sedimentation rate.
66
Increased ESR (erythrocyte sedimentation rate) is seen in...
infxns autoimmune diseases malignant neoplasms GI disease (UC) pregnancy
67
Decreased ESR is seen in...
polycythemia sickle cell anemia CHF microcytosis hypofibrinogenemia
68
Acanthocyte (spur cell)
-liver disease -abetalipoproteinemia (states of cholesterol dysregulation)
69
Basophilic stippling
-anemia of chronic disease -alcohol abuse -lead poisoning -thalassemias
70
Bite cell
G6PD deficiency
71
Elliptocyte
Hereditary elliptocytosis
72
Macro-ovalocyte
megaloblastic anemia (also hypersegmented PMNs) marrow failure
73
Ringed sideroblast
sideroblastic anemia (excess iron in mitochondria)
74
Schistocyte/helmet cell
DIC TTP/HUS traumatic hemolysis (mechanical heart valve prosthesis)
75
Spherocyte
hereditary spherocytosis autoimmune hemolysis
76
Teradrop cell
bone marrow infiltration (myelofibrosis) \*RBCs shed a tear bc they have been forced out of their home in the bone marrow.
77
Target cells
HbC disease Asplenia Liver disease Thalassemia
78
Heinz bodies are seen in...
G6PD deficiency; Heinz body-like inclusions are seen in alpha-thalassemia.
79
Heinz bodies cause....
oxidation of Hb sulfhydryl groups leading to denatured Hb precipitation and phagocytic damage to the RBC membrane forming bite cells.
80
Heinz bodies are visualized with...
special stains such as crystal violet.
81
Howell-Jolly bodies are seen in pts with...
functionl hyposplenia or asplenia.
82
Howell-Jolly bodies are...
basophilic nuclear remnants found in RBCs. They are normally removed from RBCs by splenic macrophages.
83
Iron deficiency can be caused by...
chronic bleeding, malnutrition/absorption disorders, pregnancy
84
Iron deficiency decreases...
the final step in heme synthesis leading to a microcytic, hypochromic anemia.
85
Findings in Iron Deficiency Anemia
-decreased iron -increased TIBC -decreased ferritin -fatigue -conjunctival pallor
86
Iron Deficiency Anemia may manifest as...
Plummer-Vinson syndrome which is a triad of: 1. iron deficiency anemia 2. esophageal webs 3. atrophic glossitis
87
alpha-thalassemia has a defect in...
alpha-globin gene (deletions) leading to decreased synthesis.
88
cis alpha-thalassemia deletion is prevalent in...
Asian populations. The trans deletion is prevalent in African populations.
89
alpha-thalassemia (4 allele deletion):
-no alpha-globin -excess gamma globin forms gamma4 (Hb Barts) -incompatible with life (hydrops fetalis)
90
alpha-thalassemia (3 allele deletion):
-HbH diseae -very little alpha globin -excess beta-globin forms beta4 (HbH)
91
alpha-thalassemia (1-2 allele deletion):
no clinically significant anemia
92
Beta-thalassemia is...
a microcytic, hypochrmoic anemia due to point mutations in splice sites and promoter sites leading to decreased beta-globin synthesis; prevalent in mediterranean populations
93
Beta-thalassemia minor (heterozygote) features
-beta chain underproduced -usually asymptomatic -diagnosis confirmed by increased HbA2 (\> 3.5%) on electrophoresis
94
Beta-thalassemia major (homozygote) features
-beta chain absent (severe anemia requiring blood transfusion) -marrow expansion ("crew cut" on skull x-ray) leading to skeletal deformities (chipmunk facies) -extramedullary hematopoiesis (hepatosplenomegaly)
95
Beta-thalassemia major pts are at increased risk for...
parvovirus B-19 induced aplastic crisis.
96
Beta-thalassemia major has increased...
HbF which is protective for the 1st 6 months of life (no symptoms).
97
HbS/beta-thalassemia heterozygote
mild/moderate sickle cell depending on amount of beta-globin production
98
Lead inhibits...
ferrochelatase and ALA dehydratase leading to decreased heme synthesis and increased RBC protoprophyrin;
99
Lead also inhibits...
rRNA degradation causing RBCs to retain aggregates of rRNA (basophilic stippling).
100
High risk of lead poisoning in...
old houses with chipped paint.
101
Lead poisoning findings
-lead lines on gingivae and long bones -encephalopathy -erythocyte basophilic stippling -abdominal colic -sideroblastic anemia -wrist and foot drop
102
1st line treatment for lead poisoning is...
Dimercaprol and EDTA.
103
In kids with lead poisoning, treatment is...
Succimer for chelation. (It SUCks to be a kid who eats lead.)
104
Sideroblastic Anemia is due to...
a defect in heme synthesis.
105
Hereditary sideroblastic anemia
X-linked defect in delta-ALA synthase gene
106
Causes of sideroblastic anemia
-genetic -acquired -alcohol -lead -vitamin B6 deficiency -copper deficiency -isoniazid
107
Sideroblastic Anemia presents with
-increased iron -normal TIBC -increased ferriting -ringed sideroblasts (w/ iron-laden mitochondria)
108
Treatment for sideroblastic anemia
pyridoxine (B6 - cofactor for delta-ALA synthase)
109
Megaloblastic anemia is due to...
impaired DNA synthesis. This causes the maturation of the nucleus of precursor cells in bone marrow to be delayed relative to the maturation of the cytoplasm. This causes abnormal cell division leading to pancytopenia.
110
3 types of megaloblastic anemia
-folate deficiency -B12 deficiency -orotic aciduria
111
Causes of folate deficiency megaloblastic anemia
-malnutrition (alcoholics) -malabsorption -anifolates (methotrexate, trimethoprim, phenytoin) -increased requirement (hemolytic anemia, pregnancy)
112
Findings of Folate deficiency
-hypersegmented neutrophils -glossitis -decreased folate -increased homocysteine but normal methylmalonic acid -NO neuro symptoms (distinguishes from B12 deficiency)
113
Causes of B12 deficiency anemia
-insufficient intake (vegans) -malabsorption -pernicious anemia -Diphyllobothrium latum -proton pump inhibitors
114
Findings of B12 Deficiency
-hypersegmented neutrophils -glossitis -decreased B12 -increased homocysteine -increased methylmalonic acid -neuro symptoms
115
Neurologic symptoms of B12 deficiency are due to..
subacute combined degeneration due to involvement of B12 in fatty acid pathways and myelin synthesis.
116
Neuro symptoms of B12 Deficiency
1. peripheral neuropathy w/ sensorimotor dysfunction 2. dorsal columns (vibration/proprioception) 3. lateral corticospinal (spasticity) 4. dementia
117
Orotic aciduria is due to...
the inability to convert orotic acid to UMP because of a defect in UMP synthase.
118
Orotic aciduria presents in...
children as megalobastic anemia that cannot be cured by folate or B12 with FTT.
119
Orotic aciduria does not have...
hyperammonemia (which distinguishes it from ornithine transcarbamylase deficiency).
120
Findings of Orotic Aciduria
-hypersegmented neutrophils -glossitis -orotic acid in urine
121
Treatment for Orotic Aciduria
uridine monophosphate to bypass the mutated enzyme
122
Causes of nonmegaloblatic, macrocytic anemia
-liver disease -alcoholism -reticulocytosis -drugs (5-FU, zidovudine, hydroxyurea)
123
Findings of nonmegaloblastic, macrocytic anemias
macrocytosis bone marrow suppression
124
Normocytic, normochromic anemias are classified as either...
hemolytic or nonhemolytic.
125
Findings of Intravascular Hemolysis
-decreased haptoglobin -increaesed LDH -schistocytes -increased reticulocytes -urobilinogen in the urine
126
Finings of Extravascular Hemolysis
-macrophages in the spleen clear RBCs -spherocytes -increased LDH -increased unconjugated bilirubin
127
Nonhemolytic, hormocytic anemias (3)
1. anemia of chronic disease 2. aplastic anemia 3. chronic kidney disease
128
In Anemia of Chronic Disease, inflammation leads to..
increased hepcidin (released by the liver, binds ferroportin on intestinal mucosal cells, thus inhibiting iron transport) leading to decreased release of iron from macrophages.
129
Findings of Anemia of Chronic Disease
-decreased iron -decreased TIBC -increased ferritin
130
Aplastic anemia is caused by...
failure or destruction of myeloid stem cells due to: -radiation and drugs (benzene, chloramphenicol, alkylating agents, antimetabolites) -viral agents (parvovirus B19, EBV, HIV, HCV) -Fanconi anemia -
131
Findings of Aplastic Anemia
-pancytopenia characterized by severe anemia, leukopenia and thrombocytopenia -normal cell morphology -hypocellular bone marrow with fatty infilration (dry bonemarrow tap)
132
Symptoms of Aplastic Anemia
-fatigue -malaise -purpura -mucosal bleeding -petechiae -infxn
133
Treatment of aplastic anemia
-immunosuppressive regimens -allogeneic bone marrow transplant -RBC/platelet transfusion -G-CSF -GM-CSF
134
Chronic kidney disease causes anemia because...
decreaed EPO leads to decreased hematopoiesis.
135
Types of Intrinsic Hemolytic Normocytic Anemia
-Hereditary spherocytosis (E) -G6PD deficiency (I/E) -Pyruvate kinase deficiency (E) -HbC defect (E) -Paroxysmal nocturnal hemoglobinuria (I) -Sickle Cell Anemia (E)
136
Hereditary spherocytosis is due to a defect in...
proteins interacting with RBC membrane skeleton and plasma membrane (ankyrin, band 3, protein 4.2, spectrin)
137
In hereditary spherocytosis, less membrane causes...
small and round RBCs with no central pallor (increased MCHC and increased red cell distribution width) leading to premature removal of RBCs by the spleen.
138
Findings in hereditary spherocytosis
-splenomegaly -aplastic crisis (w/ parvovirus B19 infxn)
139
Labs of Hereditary spherocytosis
-osmotic fragility test positive -eosin-5-maleimide binding test useful for screening -normal/decreased MCV with abundance of cells
140
Hereditary spherocytosis masks...
microcytia.
141
Treatment for hereditary spherocytosis
splenectomy
142
The most common enzymatic disorder of RBCs is...
G6PD deficiency (X-linked).
143
In G6PD deficiency, a defect in G6PD leads to...
decreased glutathione leading to increased RBC susceptibility to oxidant stress. Then there is hemolytic anemia followng oxidant stress.
144
In G6PD deficiency, classic causes of oxidant stress are...
sulfa drugs, antimalarials, infxns, fava beans.
145
Findings of G6PD deficiency
-back pain -hemoglobinuria a few days after oxidant stress
146
Labs for G6PD deficiency
RBCs with Heniz bodies and bite cells
147
Pyruvate kinase deficiency has a defect in...
pyruvate kinase which leads to decreased ATP and rigid RBCs.
148
Pyruvate kinase deficiency presents as...
hemolytic anemia in a newborn.
149
HbC defect is due to a...
glutamic acid to lysine mutation at residue 6 in the beta-globin.
150
HbC defect pts with HbSC (1 of each mutant gene) have...
milder disease than HbSS pts have.
151
Paroxysmal nocturnal hemoglobinuria is an...
acquired mutation in a hematopoietic stem cell leading to increased complement-mediated RBC lysis (there is impaired synthesis of GPI anchor for decay-accelerating factor that protects RBC membrane from complement).
152
Paroxysmal nocturnal hemoglobinuria has increased incidence of...
acute leukemias.
153
Triad of Paroxysmal nocturnal hemoglobinuria
-Coombs negative hemolytic anemia -pancytopenia -venous thrombosis
154
Labs for Paroxysmal Nocturanl Hemoglobinuria
-CD55/59 negative RBCs on flow cytometry
155
Treatment for Paroxysmal Nocturnal Hemoglobinuria
Eculizumab
156
Sickle Cell Anemia has a...
HbS point mutation that causes a single amino acid replacement in the beta-chain (substitution of gluatmic acid with valine) at position 6.
157
Pathogenesis of Sickle Cell Anemia
low O2, dehydration or acidosis preciptates sickling (deoxygenated HbS polymerizes) which results in amemia and vaso-occlusive disease
158
Newborns with sickle cell are initially...
asymptomatic because of increased HbF and decreased HbS.
159
Heterozygotes (sickle cell trait) have...
resistance to malaria.
160
On skull x-ray, sickle cell shows...
"crew cut" due to marrow expansion from increased erythropoiesis (also in thalassemias).
161
Complications in sickle cell
-aplastic crisis (due to parvovirus B19) -autosplenectomy (increased risk of infxn with encapsulated organisms) -splenic sequestration crisis -salmonella osteomyelitis -dactylitis (painful hand swelling) -acute chest syndrome -avascular necrosis -stroke -renal papillary necrosis -microhematuria
162
Diagnosis of sickle cell is made with...
hemoglobin electrophoresis
163
Treatment of sickle cells
hydroxyurea (increases HbF) bone marrow transplant
164
Extrinsic Hemolytic normocytic anemias
1. autoimmune hemolytic anemia 2. microangiopathic anemia 3. macroangiopathic anemia 4. infxn
165
Autoimmune hemolytic anemia with warm agglutinin is...
chronic anemia seen in SLE, CLL or with certain drugs (alpha-methyldopa). IgG mediated.
166
Autoimmune hemolytic anemia (AIHA) with cold agglutinin is seen with...
acute anemia triggered by cold; seen in CLL, mycoplasma penumonia infections or infectious mononucleosis
167
AIHAs are usually positive for...
Coombs.
168
Direct Coombs Test
anti-Ig antibody added to pts blood; RBCs agglutinate if RBCs are coated with Ig
169
Indirect Coombs Test
normal RBCs added to pts serum; if serum has anti-RBC surface Ig, RBCs agglutinate when anti-Ig antibodies are added.
170
Microangiopathic anemia pathogenesis
RBCs are damaged when passing through obstructed or narrowed vessel lumina
171
Microangiopathic anemia is seen in...
DIC, TTP-HUS, SLE and malignant HTN.
172
On blood smear of microangiopathic anemia, there are...
schistocytes (helmet cells) due to mechanical destruction of RBCs.
173
Macroangiopathic anemia is due to...
prosthetic heart valves and aortic stenosis secondary to mechanical damage. Show schistocytes.
174
Infections can increase the...
destruction of RBCs (malaria, Babesia).
175
Transferrin
transports iron in the blood
176
Ferritin
primary iron storage protein of the body
177
Neutropenia definition
absolute neutrophil count \< 1500
178
Neutropenia causes
-sepsis/postinfection -drugs -aplastic anemia -SLE -radiation
179
Lymphopenia definition
absolute lymphocyte count \< 1500
180
Causes of lymphopenia
-HIV -DiGeorge syndrome -SCID -SLE -corticosteroids -radiation -sepsis -postoperative
181
Eosinopenia causes
-cushing syndrome -corticosteroids
182
Corticosteroids cause neutrophilia because they...
decrease activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation.
183
Corticosteroids cause eosinopenia and lymphopenia becasue they...
sequester eosinophils in LNs and cause apoptosis of lymphocytes.
184
The porphyrias are...
conditions of defective heme synthesis that lead to accumulation of heme precursor. (lead inhibits enzymes of heme synthesis, leading to similar conditions)
185
Affected enzyme in lead poisoning
-ferrochelatase -ALA dehydratase
186
Accumulated substrate in lead posioning
-protoporphyrin -delta-ALA (in blood)
187
Presenting symptoms of Lead poisoning
-microcytic anemia -GI/kidney disease
188
Common presentation of lead poisoning in children
Exposure to lead point leads to mental deterioration.
189
Common presentation of lead poisoning in adults
environmental exposure (battery/ammunition/radiator factory) leads to HA, memory loss, demyelination)
190
Affected enzyme in acute intermittent porphyria
porphobilinogen deaminase
191
Accumulated substrate in acute intermittent porphyria
-porphobilinogen -delta-ALA -coporphobilinogen (urine)
192
Presenting symptoms of acute intermittent porphyria
-painful abdomen -port-wine colored urine -polyneuropathy -pscyhological disorders -precipitated by drugs, alcohol and starvation (5 Ps)
193
Treatment for acute intermittent porphyria
-glucose and heme (which inhibit ALA synthase)
194
Affected enzyme in Porphyria cutanea tarda
uroporphyrinogen decarboxylase
195
Accumulated substrate in Porphyria cutanea tarda
uroporphyrin (tea-colored urine)
196
Presenting symptom of Porphyria cutanea tarda
blistering cutaneous photosensitivity tea-colored urine
197
Prothrombin Time (PT) tests...
the function of the common and extrinsic pathway (factors I, II, V, VII, and X); a defect will increase PT.
198
PTT tests...
function of common and intrinsic pathway (all factors exceptr VII and XIII); defect will increase PTT.
199
Hemophilia A features
-increased PTT -deficiency of factor VIII
200
Hemophilia B features
-increased PTT -deficiency of factor IX
201
Clinical findings of Hemophilia A and B
-hemarthroses (bleeding into joints) -easy bruising
202
Treatment for Hemophilia A
-recmobinant factor VIII
203
Vitamin K deficiency features
-increased PT -increased PTT -bleeding time is normal -decreased synthesis of factors II, VII, IX, X, protein C and protein S
204
Defects in platelet plug formation leads to...
increased bleeding time
205
Platelet abnormalities lead to...
microhemorrhage: mucous membrane bleeding (epistaxis), petechiae/purpura, increased bleeding time, decreased platelet count
206
Bernard-Soulier Syndrome Featuers
-increaed bleeding time -decreased platelets -decreased GpIb (leads to defect in platelet to vWF adhesion)
207
Glanzmann thrombasthenia features
-increased bleeding time -decreased GpIIb/IIIa (defect in platelet to platelet aggregation) -blood smear shows no platelet clumping
208
Immune thrombocytopenia
-decreased platelets -increased bleeding time -anti-GpIIb/IIIa antibodies (splenic macrophage consumes platelet/Ab complex) -may be triggered by viral illness -increased megakaryocytes on bone marrow biopsy
209
Thrombotic thrombocytopenic pupura (TTP) features
-decreased platelets -increased bleeding time -deficiency of ADAMTS 13 leads to decreased degradation of vWF multimers
210
In TTP, with the increased large vWF multimers, it leads to...
increased platelet adhesion and increased platelet aggregation and thrombosis.
211
Labs of TTP
schistocytes, increased LDH
212
Symptoms of TTP
-pentad of neurologic and renal symptoms, fever, thrombocytopenia and microangiopathic hemolytic anemia (FATRN)
213
Treatment for TTP
exchange transfusion and steroids
214
von Willebrand Disease features
-increased bleeding time -normal/increased PTT -decreased vWF causes a defect in platelet-to-vWF adhesion
215
Characteristics of von Willebrand Disease
-mild -autosomal dominant
216
Diagnose von Willebrand Disease with...
ristocetin cofactor assay (decreased agglutination is diagonistic).
217
Treatment for von Willebrand Disease
DDAVP (desmopressin) which releases vWF stored in endothelium
218
DIC features
-decreased platelets -increased bleeding time -increased PT -increased PTT
219
DIC is...
widespread activation of clotting which leads to a deficiency in clotting factors which creates a bleeding state.
220
Causes of DIC
Sepsis (gram-negative) Trauma Obstetric complications acute Pancreatitis Malignancy Nephrotic syndrome Transfusion (STOP Making New Thrombi)
221
Labs for DIC
-schistocytes -increased fibrin split products (D-dimers) -decreased fibrinogen -decreased factors V and VIII
222
vWF acts to...
carry/protect factor VIII
223
Factor V Leiden is production of...
mutatn factor V that is resistant to degradation by activated protein C.
224
Hereditary thrombosis sydnromes leading to hypercoaguability
1. Factor V Leiden 2. Prothrombin gene mutation 3. Antithrombin deficiency 4. Protein C or S deficiency
225
Prothrombin Gene Mutation is in the...
3' untranslated region leading to increased production of prothrombin leading to venous clots.
226
Antithrombin deficiency is inherited and has no direct effect on...
PT, PTT or thrombin time but diminshes the increase in PTT following heparin administration.
227
Antithrombin deficiency can also be acquired when...
renal failure leads to antithrombin loss in the urine leading to increased factors II and X.
228
Protein C or S deficiency leads to decreased ability to...
inactivate factors V and VIII leading to increased risk of thrombotic skin necrosis with hemorrhage following administration of warfarin.
229
Packed RBCs effect
increase Hb and O2 carrying capacity
230
Packed RBCs clinical use
acute blood loss severe anemia
231
Platelets transfusion clinical use
stop significant bleeding (thrombocytopenia)
232
Fresh frozen plasma transfusion effect
increase coagulation factors
233
FFP transfusion clinical use
DIC cirrhosis warfarin overdose exchange transfusion in TTP/HUS
234
Cryoprecipitate transfusion effect
contains fibrinogen, factor VIII, factor XIII, vWF and fibronectin
235
Clincial use of cryoprecipitate transfusion
treat coagulation factor deficiencies involving fibrinogen and factor VIII
236
Blood transfusion risks include..
infection transmission transfuscion reactions iron overload hypocalcemia hyperkalemia
237
Leukemia
lymphoi or myeloid neoplasms with widespread involvement of bone marrow; tumor cells are usually found in peripheral blood
238
Lymphoma
discrete tumor masses arising from LNs
239
Leukemoid rxn is an...
acute inflammatory response to infection.
240
Features of the Leukemoid Reaction
-increased WBC -increased neutrophils and band cells -increased leukocyte ALP
241
Hodgkin Lymphoma
localized, single group of nodes; extranodal is rare; contiguous spread; better prognosis
242
Hodgkin Lymphoma is characterized by...
Reed-Sternberg cells.
243
Distribution of Hodgkin Lymphoma is...
bimodal: young adulthood and greater than 55. Usually in men.
244
50% of Hodgkin Lymphoma is associated with...
EBV.
245
Symptoms of Hodgkin's
-contitutional (B) symptoms - low fever, night sweats, weight loss
246
Non-Hodgkin lymphoma
-multiple, peripheral nodes -extranodal involvement common -noncontiguous spread
247
The majority of Non-Hodgkin lymphomas involve...
B cells.
248
Peak incidence for Non-Hodgkin's is...
20-40.
249
Non-Hodgkin's lymphom may be associated with...
HIV and immunosuppression.
250
Reed-Sternberg cells
-binucleate -CD15 and CD30 + -B cell origin -necessary for diagnosis of Hodgkin Lymphoma
251
Forms of Hodgkin lymphoma
-nodular sclerosing form most common -lymphocyte-rich has best prognosis
252
Neoplasms of mature B cells (Non-Hodgkin lymphomas)
1. Burkitt 2. Diffuse large B-cell 3. Mantle Cell 4. Follicular
253
Burkitt lymphoma occurs in...
adolescents.
254
Burkitt lymphoma genetics
t(8;14) translocation of c-myc and heavy-chain Ig
255
Histology of Burkitt
-"starry sky" appearance -sheets of lymphocytes w/ interspersed macrophages
256
Burkitt is associated with...
EBV
257
Different forms of Burkitt
Endemic form: jaw lesion, Africa Sporadic form: pelvis or abdomen
258
Diffuse large B-cell lymphoma (DLBL) occurs in...
older adults usually.
259
Genetics of Diffuse large B-cell lymphoma
t(14;18)
260
Mantle cell lymphoma occurs in...
older males.
261
Mantle cell lymphoma genetics
t(11;14) translocation of cyclin D1 and heavy chain Ig
262
Mantle cell lymphoma cell marker
CD5+
263
Follicular lymphoma is seen in...
adults.
264
Genetics of follicular lymphoma
t(14;18) translocation of heavy chain Ig and bcl-2
265
bcl-2 inhibits...
apoptosis.
266
Follicular lymphoma presents with...
painless "waxing and waning" lymphadenopathy.
267
Neoplasms of mature T cells (non-hodgkin lymphoma)
\*see cutaneous lesions in adults 1. Adult T-cell lymphoma 2. Mycosis fungoides/Sezary syndrome
268
Adult T-cell lymphoma is caused by...
HTLV-1 and is associated with IV drug abuse.
269
Presentation of Adult T-cell lymphoma
-cutaneous lesions -esp. in Japan, West Africa and Caribbean -lytic bone lesions and hypercalcemia
270
Presentation of Mycosis fungoides/Sezary syndrome
-adults present with cutaneous patches/plaques/tumors with potential to spread to LNs and viscera -circulating malignant cells -CD4+
271
Multiple myeloma is a...
monoclonal plasma cell ("fried egg" appearance) cancer that arises in the marrow and produces large amounts of IgG and IgA.
272
Multiple myeloma is associated with...
-increased susceptiblity to infection -primary amyloidosis -punched out lytic bone lesions -M spike on serum protein electrophoresis -Ig light chains in urine (Bence Jones protein) -Rouleaux formation (stacked RBCs)
273
Histology of Multiple myeloma
-numerous plasma cells with "clock face" chromatin -intracytoplasmic inclusions containing Ig
274
Waldenstrom macroglobulinemia is similar to Multiple myeloma except...
M spike is from IgM and there are no lytic bone lesions.
275
Monoclonal gammopathy of undetermined significance (MGUS)
monoclonal expansion of plasma cells with M spike and decreased plamsa cells in bone marrow \*\*asymptomatic precursor to multiple myeloma
276
Myelodysplastic syndromes are...
stem cell disorders involving ineffective hematopoiesis leading to defects in cell maturation of all non-lymphoid lineages.
277
Myelodysplastic syndromes are caused by...
de novo mutations or environmental exposure (radiation, benzene, chemo).
278
Myelodysplastic syndrome has a risk of trasnformation to..
AML.
279
Pseudo-Pelger-Huet anomaly
neutrophils with bilobed nuclei typically seen after chemo
280
Acute lymphoblastic leukemia/lymphoma (ALL) is seen in those...
less than 15.
281
T-cell ALL can present as a...
mediastinal mass (leukemic infiltration of the thymus).
282
ALL is associated with...
Down Syndrome.
283
Markers of ALL
-increased lymphoblasts in blood and marrow -TdT+ -CD10+
284
ALL other features
-responsive to therapy -may spread to CNS and testes -t(12;21) = better prognosis
285
In leukemias, unregulated growth of...
leukocytes in bone marrow leads to anemia, infxns and hemorrhage.
286
Small lymphocytic lymphoma or Chronic lymphocytic lymphoma (SLL/CLL) features
-age \> 60 yrs -CD20+ -CD5+ -B cells -progresses slowly -smudge cells -AIHA
287
SLL is the same as CLL except CLL has...
increased peripheral blood lymphocytosis or bone marrow invovlement.
288
Hairy Cell Leukemia features
-adults -B cells -cells have filamentous, hair-like projections
289
Hairy cell leukemia stains...
TRAP positive.
290
Hairy cell leukemia causes...
marrow fibrosis (dry tap).
291
Treatment for Hairy cell
-cladribine (an adenosine analog that inhibits adenosine deaminase)
292
Acute myelogenous leukemia (AML) features
-65 yrs -auer rods -peroxidase + -increased circulating myeloblasts
293
Risk factors for AML
-alkylating chemo -radiation -myeloproliferative disorders -down syndrome
294
M3 type of AML has...
a t(15;17) translocation.
295
M3 subtype of AML responds to...
all trans retinoic acid (vitamin A) which induces differentiation of myeloblasts.
296
Common presentation of AML is...
DIC which is induced by chemo due to release of Auer rods.
297
Chronic myelogenous leukemia (CML)
-45-85 yrs -philadelphia chromosome t(9;22) - bcr-abl -myeloid stem cell proliferation -increased neutrophils, metamyeloctyes and basophils -splenomegaly
298
CML may progress to...
AML or ALL ("blast crisis").
299
As a result of low activity in the granulocytes, CML has a very low level of...
leukocyte alkaline phosphatase.
300
CML responds to...
imatinib (an inhibitor of the bcr-abl tyrosine kinase).
301
Langerhans cell histiocytosis is a proliferative disorder of...
dendritic cells from a monocyte lineage that presents in a child as lytic bone lesions and skin rash. Or recurrent otitis media with a mass involving the mastoid bone.
302
In langerhans cell histiocytosis, the cells are...
functionally immature and do not efficiently stimulate the primary T lymphocytes via Ag presentation.
303
Langerhans cell histiocytosis cells express...
S-100 (mesodermal origin) and CD1a. Birbeck granules (tennis rackets) are characteristic.
304
Polycythemia vera features
-hematocrit \> 55% -mutation in JAK2
305
Polycythemia vera presents as...
intense itching after hot shower. Classic symptom is erythromelalgia (severe, burning pain and red/blue color) due to episodic clots in extremities.
306
Secondary polycythemia is via...
natural or artificial increase in EPO.
307
Essential thrombocytosis is similar to polycythemia vera but is specific for...
overproduction of abnormal platelets leading to... bleedign and thrombosis. The bone marrow contains enlarged megakaryocytes.
308
Myelofibrosis is...
fibrotic obliteration of the bone marrow. Teardrop RBCs and immature forms of the myeloid line are seen.
309
bcr-abl transformation in CML leads to...
increased cell division and inhibition of apoptosis.
